Design of a multi-signature ensemble classifier predicting neuroblastoma patients' outcome

<p>Abstract</p> <p>Background</p> <p>Neuroblastoma is the most common pediatric solid tumor of the sympathetic nervous system. Development of improved predictive tools for patients stratification is a crucial requirement for neuroblastoma therapy. Several studies utilized gene expression-based signatures to stratify neuroblastoma patients and demonstrated a clear advantage of adding genomic analysis to risk assessment. There is little overlapping among signatures and merging their prognostic potential would be advantageous. Here, we describe a new strategy to merge published neuroblastoma related gene signatures into a single, highly accurate, Multi-Signature Ensemble (MuSE)-classifier of neuroblastoma (NB) patients outcome.</p> <p>Methods</p> <p>Gene expression profiles of 182 neuroblastoma tumors, subdivided into three independent datasets, were used in the various phases of development and validation of neuroblastoma NB-MuSE-classifier. Thirty three signatures were evaluated for patients' outcome prediction using 22 classification algorithms each and generating 726 classifiers and prediction results. The best-performing algorithm for each signature was selected, validated on an independent dataset and the 20 signatures performing with an accuracy > = 80% were retained.</p> <p>Results</p> <p>We combined the 20 predictions associated to the corresponding signatures through the selection of the best performing algorithm into a single outcome predictor. The best performance was obtained by the Decision Table algorithm that produced the NB-MuSE-classifier characterized by an external validation accuracy of 94%. Kaplan-Meier curves and log-rank test demonstrated that patients with good and poor outcome prediction by the NB-MuSE-classifier have a significantly different survival (p < 0.0001). Survival curves constructed on subgroups of patients divided on the bases of known prognostic marker suggested an excellent stratification of localized and stage 4s tumors but more data are needed to prove this point.</p> <p>Conclusions</p> <p>The NB-MuSE-classifier is based on an ensemble approach that merges twenty heterogeneous, neuroblastoma-related gene signatures to blend their discriminating power, rather than numeric values, into a single, highly accurate patients' outcome predictor. The novelty of our approach derives from the way to integrate the gene expression signatures, by optimally associating them with a single paradigm ultimately integrated into a single classifier. This model can be exported to other types of cancer and to diseases for which dedicated databases exist.</p

Molecular cancer classification using an meta-sample-based regularized robust coding method

Motivation Previous studies have demonstrated that machine learning based molecular cancer classification using gene expression profiling (GEP) data is promising for the clinic diagnosis and treatment of cancer. Novel classification methods with high efficiency and prediction accuracy are still needed to deal with high dimensionality and small sample size of typical GEP data. Recently the sparse representation (SR) method has been successfully applied to the cancer classification. Nevertheless, its efficiency needs to be improved when analyzing large-scale GEP data. Results In this paper we present the meta-sample-based regularized robust coding classification (MRRCC), a novel effective cancer classification technique that combines the idea of meta-sample-based cluster method with regularized robust coding (RRC) method. It assumes that the coding residual and the coding coefficient are respectively independent and identically distributed. Similar to meta-sample-based SR classification (MSRC), MRRCC extracts a set of meta-samples from the training samples, and then encodes a testing sample as the sparse linear combination of these meta-samples. The representation fidelity is measured by the l2-norm or l1-norm of the coding residual. Conclusions Extensive experiments on publicly available GEP datasets demonstrate that the proposed method is more efficient while its prediction accuracy is equivalent to existing MSRC-based methods and better than other state-of-the-art dimension reduction based methods.This article was funded by the National Science Foundation of China on finding tumor-related driver pathway with comprehensive analysis method based on next-generation sequencing data and the dimension reduction of gene expression data based on heuristic method (grant nos. 61474267, 60973153 and 61133010) and the National Institutes of Health (NIH) Grant P01 AG12993 (PI: E. Michaelis). This article has been published as part of BMC Bioinformatics Volume 15 Supplement 15, 2014: Proceedings of the 2013 International Conference on Intelligent Computing (ICIC 2013). The full contents of the supplement are available online at http://www.biomedcentral.com/bmcbioinformatics/supplements/15/S15

Selección de Características de Microarreglos de ADN Utilizando una Búsqueda Cuckoo

En este artículo, se propone un método híbrido para la selección y clasificación de datos de microarreglos de AND. Primero, el método combina los subconjuntos de genes relevantes obtenidos de cinco métodos de filtro, después, se implementa un algoritmo basado en una búsqueda cuckoo combinado con un clasificador MSV. El algoritmo híbrido explora dentro del subconjunto obtenido en la etapa anterior y selecciona los genes que alcanzan un alto desempeño al entrenar al clasificador. En los resultados experimentales, el algoritmo obtiene una tasa de clasificación alta seleccionado un número pequeño de genes, los resultados obtenidos son comparados con otros métodos reportados en la literatura

Feature Space Modeling for Accurate and Efficient Learning From Non-Stationary Data

A non-stationary dataset is one whose statistical properties such as the mean, variance, correlation, probability distribution, etc. change over a specific interval of time. On the contrary, a stationary dataset is one whose statistical properties remain constant over time. Apart from the volatile statistical properties, non-stationary data poses other challenges such as time and memory management due to the limitation of computational resources mostly caused by the recent advancements in data collection technologies which generate a variety of data at an alarming pace and volume. Additionally, when the collected data is complex, managing data complexity, emerging from its dimensionality and heterogeneity, can pose another challenge for effective computational learning. The problem is to enable accurate and efficient learning from non-stationary data in a continuous fashion over time while facing and managing the critical challenges of time, memory, concept change, and complexity simultaneously. Feature space modeling is one of the most effective solutions to address this problem. For non-stationary data, selecting relevant features is even more critical than stationary data due to the reduction of feature dimension which can ensure the best use a computational resource to produce higher accuracy and efficiency by data mining algorithms. In this dissertation, we investigated a variety of feature space modeling techniques to improve the overall performance of data mining algorithms. In particular, we built Relief based feature sub selection method in combination with data complexity iv analysis to improve the classification performance using ovarian cancer image data collected in a non-stationary batch mode. We also collected time series health sensor data in a streaming environment and deployed feature space transformation using Singular Value Decomposition (SVD). This led to reduced dimensionality of feature space resulting in better accuracy and efficiency produced by Density Ration Estimation Method in identifying potential change points in data over time. We have also built an unsupervised feature space modeling using matrix factorization and Lasso Regression which was successfully deployed in conjugate with Relative Density Ratio Estimation to address the botnet attacks in a non-stationary environment. Relief based feature model improved 16% accuracy of Fuzzy Forest classifier. For change detection framework, we observed 9% improvement in accuracy for PCA feature transformation. Due to the unsupervised feature selection model, for 2% and 5% malicious traffic ratio, the proposed botnet detection framework exhibited average 20% better accuracy than One Class Support Vector Machine (OSVM) and average 25% better accuracy than Autoencoder. All these results successfully demonstrate the effectives of these feature space models. The fundamental theme that repeats itself in this dissertation is about modeling efficient feature space to improve both accuracy and efficiency of selected data mining models. Every contribution in this dissertation has been subsequently and successfully employed to capitalize on those advantages to solve real-world problems. Our work bridges the concepts from multiple disciplines ineffective and surprising ways, leading to new insights, new frameworks, and ultimately to a cross-production of diverse fields like mathematics, statistics, and data mining

Computational Intelligence in Healthcare

This book is a printed edition of the Special Issue Computational Intelligence in Healthcare that was published in Electronic